Estrogen-related receptor alpha
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| Location (UCSC) | Chr 11: 64.31 – 64.32 Mb | n/a | |||||||
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Estrogen-related receptor alpha (ERRα), also known as NR3B1 (nuclear receptor subfamily 3, group B, member 1), is a
NR3A1),[4] but subsequent ligand binding and reporter-gene transfection experiments demonstrated that estrogens did not regulate ERRα.[5] Currently, ERRα is considered an orphan nuclear receptor.[4][5]
Tissue distribution
ERRα has wide tissue distribution but it is most highly expressed in tissues that preferentially use fatty acids as energy sources such as
intestine, and skeletal muscle.[6] Recently, ERRα has been detected in normal adrenal cortex tissues, in which its expression is possibly related to adrenal development, with a possible role in fetal adrenal function, in DHEAS production in adrenarche, and also in steroid production of post-adrenarche/adult life.[7]
Function
The
CYP11B1 and CYP11B2, which indicates that this nuclear receptor may be required for the production of cortisol and aldosterone in the adrenal gland.[12]
Metabolism
ERRα regulates genes involved in
knockout mice suggested that this receptor, while dispensable for basal cellular function, is definitely necessary to provide the levels of energy necessary to respond to physiological and pathological insults in diverse tissues,[5] the lack of that nuclear receptor leading to impaired fat metabolism and absorption.[20]
Estrogen signaling
Estrogen receptor alpha (ERα) and estrogen-related receptor alpha (ERRα) have been found to regulate many of the same genes.[21][22] Furthermore, ERRα appears to modulate the activity of ERα in various tissues including breast, uterus, and bone.[23]
Ligands
No
endogenous ligands of ERRα have been identified to date, hence ERRα is classified as an orphan receptor. In addition both biochemical and structural studies indicate that ERRα is constitutively active in the absence of ligand.[24] ERRα does, however, interact with the metabolic-inducible coactivator PGC1-α
in its AF2 region which is sometimes referred to as the "protein ligand" of ERRα.
The
XCT790 has been identified as a potent and selective inverse agonist of ERRα.[26] SLU-PP-332 is a potent agonist of ERRα.[27]
Cholesterol has recently been found to bind to and activate the ERRα, and may be the
knockout mice.[28] Furthermore, statin-associated myopathy and suppression of cholesterol-induced cytokine secretion by macrophages are reduced by absence or inhibition of ERRα.[28] As such, modulation of ERRα signaling is a key mediator in the actions of statins (by changes in cholesterol levels) and bisphosphonates.[28]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000173153 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: ESRRA estrogen-related receptor alpha".
- ^ S2CID 4275394.
- ^ PMID 21172432.
- PMID 16923397.
- PMID 23123734.
- PMID 15087503.
- PMID 17229846.
- PMID 9178750.
- ^ PMID 15878968.
- S2CID 140208125.
- S2CID 16143809.
- S2CID 11184579.
- PMID 15100410.
- PMID 15456881.
- PMID 17229846.
- PMID 28614293.
- ^ PMID 21731503.
- PMID 14585956.
- PMID 10319326.
- PMID 10428965.
- PMID 17259555.
- PMID 15337744.
- PMID 14638870.
- PMID 15509154.
- PMID 37739806.
- ^ PMID 26777690.
External links
- FactorBook ERRA
- Overview of all the structural information available in the PDB for UniProt: P11474 (Steroid hormone receptor ERR1) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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